An anti-wrinkle skin care composition with visible effect within seven days and its use

Abstract

The application discloses a kind of seven days can see the effect of anti-wrinkle skin care composition and its preparation method and application.The composition comprises 3-15wt% fruit acid component and 0.5-10wt% molecular weight 3-50kDa β-1,3 / 1,6-glucan, the balance is cosmetically acceptable carrier;The fruit acid component is selected from one or more of mandelic acid, p-methyl mandelic acid or p-carboxy mandelic acid, and esterification product is formed with glucan component under the condition of pH 3.0-5.0.It is preferred that p-carboxy mandelic acid is prepared by potassium permanganate oxidation, recrystallization from p-methyl mandelic acid, and the purity is ≥99%;Glucan molecular weight is preferably 5-20kDa;Degree of esterification is preferably 10-30%.The application also provides a three-step preparation process of the composition and its application in anti-wrinkle cosmetics.The composition of the application realizes the rapid anti-wrinkle effect of seven days wrinkle depth reduction ≥15% by molecular conjugation of fruit acid and glucan for the first time, with extremely low irritation, and has the outstanding characteristics of high efficiency, mildness, quick effect.

Description

Technical Field

[0001] This invention relates to the field of anti-wrinkle cosmetics, and in particular to an anti-wrinkle skin care composition that is effective within seven days and its application. Background Technology

[0002] The formation of wrinkles is a complex physiological process involving delayed epidermal renewal and dermal collagen loss. Current mainstream anti-wrinkle active ingredients primarily focus on single pathways: Vitamin A derivatives (such as retinol) and peptides work by stimulating dermal collagen synthesis, but their effects are usually slow, requiring 4-8 weeks or more, and the former can easily cause skin irritation and photosensitivity. Traditional fruit acids, such as glycolic acid and lactic acid, mainly improve skin texture by promoting epidermal keratinocyte metabolism; while they can quickly brighten the skin, their effect on dermal structural remodeling is limited, and high-concentration use is often accompanied by significant stinging, redness, and peeling. Therefore, the market urgently needs an anti-wrinkle solution that can quickly and gently act on both epidermal renewal and dermal repair pathways.

[0003] In recent years, the application of polysaccharide ingredients in skincare products has attracted much attention. Among them, β-glucan is widely used due to its excellent moisturizing, repairing, and immunomodulatory activities, but mostly as an auxiliary ingredient. Cutting-edge research indicates that certain low-molecular-weight β-glucans with specific structures not only possess biological activity themselves but may also act as carriers or reaction platforms, interacting with other active molecules. However, in existing technologies, there is a lack of systematic research on the in-situ formation of functional complexes between β-glucan and specific fruit acids under controlled conditions, and the use of these complexes to achieve rapid anti-wrinkle effects. Specifically, existing technologies have at least the following shortcomings: First, there is a lack of innovation in the mechanism of action and combination: most existing products are simple physical combinations of fruit acid and dextran, in which the two play their own roles independently in the formula. They have failed to form a composite entity with new functions through chemical or physicochemical reactions, and their synergistic effect is limited, so they cannot achieve the anti-wrinkle effect of "1+1>2".

[0004] Secondly, the selection and targeting of ingredients are not strong enough: the selection of fruit acids mostly focuses on water-soluble acids such as glycolic acid and lactic acid, which have relatively significant irritation. However, how to synergize specific fruit acid families that have both lipophilicity and mildness with dextran to achieve rapid transdermal and dermal effects has not been explored in depth.

[0005] Third, there is a lack of verification schemes for rapid effectiveness: anti-wrinkle products on the market generally require a long period of time to take effect, usually several weeks to several months. There is a lack of technical solutions and empirical data to achieve significant improvement in wrinkles in 7 days or less through precise ingredient screening, structural design and formulation process optimization. Summary of the Invention

[0006] The first objective of this application is to provide an anti-wrinkle skincare composition that is effective within seven days, with rapid anti-wrinkle effects, highly targeted ingredient selection, and innovative mechanism of action and combination.

[0007] The above-mentioned objective of this invention is achieved through the following technical solutions: An anti-wrinkle skincare composition that shows effects within seven days, comprising the following components: The fruit acid component has a content of 3-15 wt%, wherein the fruit acid component is selected from one or more of mandelic acid, p-methylmandelic acid or p-carboxymandelic acid; The content of the dextran component is 0.5-10 wt%, wherein the dextran component is β-1,3 / 1,6-glucan with a molecular weight of 3-50 kDa; The remaining amount is a carrier that is acceptable in cosmetics. The fruit acid component and the dextran component can form an esterification product under pH 3.0-5.0 conditions.

[0008] In the above technical solution, the fruit acid component is selected from one or more of mandelic acid, p-methylmandelic acid, or p-carboxymandelic acid, all of which are α-hydroxy acids with a benzene ring structure, possessing both lipophilicity and mildness: lipophilicity allows it to effectively penetrate hair follicles and the lipid barrier of the stratum corneum, while mildness stems from the slow transdermal rate caused by its large molecular weight, thus significantly reducing the irritation of traditional fruit acids; the dextran component is β-1,3 / 1,6-glucan with a molecular weight of 3-50 kDa. Dextran in this molecular weight range maintains excellent water solubility and film-forming properties, while possessing sufficient chain length and active functional groups to support fruit acid molecules. Simultaneously, it can be moderately degraded by skin surface enzymes, achieving controlled release of active ingredients; the fruit acid component and the dextran component are in harmony at pH... Under conditions of 3.0-5.0, an esterification product is formed in situ. This esterification product is a molecular-level complex bound by covalent bonds: dextran, as a hydrophilic macromolecular backbone, provides long-lasting moisturizing and barrier repair, while fruit acid, as a functional side chain, is suspended on the backbone by ester bonds. Under the action of skin esterases, it is slowly hydrolyzed and released, achieving a gentle skin-renewing effect lasting for more than 12 hours. At the same time, the esterification process significantly reduces the free concentration of fruit acid, avoiding the "shock-like" irritation of traditional fruit acids. The content of 3-15wt% fruit acid and 0.5-10wt% dextran constitutes a synergistic ratio range. Within this range, the two can form a stable complex with an esterification degree of 10-30%. If the ratio is too low, the binding is insufficient and the sustained-release effect is inadequate; if the ratio is too high, the fruit acid is released too slowly and the immediate efficacy is limited. The balance is a cosmetically acceptable carrier, ensuring that the composition can be prepared into various dosage forms, with formulation compatibility and industrial transformation prospects. The synergistic effect of the above-mentioned components and parameters enables the composition of the present invention to achieve deep integration of the keratin renewal function of fruit acid and the dermal repair function of dextran at the molecular level. As a result, when used 1-2 times a day for 7 consecutive days, the depth of wrinkles around the eyes is reduced by ≥15%, achieving a rapid anti-wrinkle effect in seven days, while controlling the irritation rating to the range of no irritation or very slight irritation.

[0009] Preferably, the mass ratio of the fruit acid component to the dextran component is 1:0.1 to 1:2.

[0010] In the above technical solution, the mass ratio of fruit acid component to dextran component is limited to 1:0.1 to 1:2. This ratio range is the synergistic efficacy window determined through orthogonal optimization experiments: when the mass ratio of fruit acid to dextran is higher than 1:0.1, the dextran backbone is insufficient to carry all fruit acid molecules, resulting in a large amount of fruit acid existing in free form, significantly reducing the efficiency of esterification product formation, impairing the sustained-release effect, increasing irritation, and making it difficult for the moisturizing and repairing effect of dextran to fully cover the barrier disturbance caused by fruit acid; when the mass ratio of fruit acid to dextran is lower than 1:2, the absolute content of fruit acid active groups in the unit mass composition is insufficient, and the density of fruit acid side chains in the esterification product is too low, resulting in a decrease in keratin renewal efficiency and failure to meet the seven-day anti-wrinkle effect; while at 1:0.1... Within the preferred ratio range of 1:2, fruit acid and dextran can form a functional conjugate with a stable degree of esterification of 10-30%. At this point, the loading efficiency and release rate of the dextran skeleton on fruit acid reach the optimal balance: ensuring sufficient density of fruit acid side chains to provide gentle skin-renewing power for more than 12 hours, while ensuring that the film-forming moisturizing and barrier repair functions of dextran are not excessively consumed. This mass ratio range, together with the fruit acid content of 3-15wt% and the dextran content of 0.5-10wt%, forms a dual numerical limit, which together constitutes the process control window for the composition of the present invention from raw material input to the degree of esterification of the final product. This allows those skilled in the art to reproduce the technical effects of a degree of esterification of 10-30%, a wrinkle reduction of ≥15% in seven days, and a non-irritating rating.

[0011] Preferably, the p-carboxymandelic acid is obtained by oxidation of p-methylmandelic acid. The oxidation reaction is carried out in an alkaline aqueous solution with a concentration of 0.5wt%-5wt% using potassium permanganate as the oxidant, at a reaction temperature of 50-80℃. The product obtained is purified by recrystallization in an acetone-water mixed solvent, and its HPLC purity is not less than 99%.

[0012] In the above technical solution, p-carboxymandelic acid is limited to preparation via a specific oxidation reaction: using p-methylmandelic acid as raw material and potassium permanganate as oxidant, a selective oxidation reaction is carried out in an alkaline aqueous solution with a concentration of 0.5wt%-5wt% at 50-80℃. The crude product is purified by recrystallization in an acetone-water mixed solvent, and the final product has an HPLC purity of not less than 99%. This preparation method is an industrial-scale adaptation process for cosmetic-grade p-carboxymandelic acid, and has the following technical advantages: p-methylmandelic acid, as a starting material, is itself a component of fruit acids and can be directly obtained from the raw material system of the composition of this invention, without the need to introduce additional intermediates, thus reducing the complexity of the raw material supply chain and quality control costs; potassium permanganate, as an oxidant, selectively oxidizes the para-methyl group of the benzene ring to a carboxyl group in a 0.5wt%-5wt% alkaline aqueous solution system, without causing racemization, over-oxidation, or side chain cleavage of the hydroxyl and carboxyl groups on the chiral α-carbon, thus completely preserving the core active structure of the α-hydroxy acid; the reaction temperature is controlled at 50-80℃. Below 50℃, the oxidation rate is too slow, and above 80℃, side reactions increase significantly. This temperature range is suitable for... The optimal balance between conversion rate >90% and selectivity >95% is achieved. Recrystallization in an acetone-water mixed solvent is a key purification step. Acetone has moderate solubility for the target product, and water, as an antisolvent, allows for precise control of the crystallization curve. A single recrystallization can increase the purity from 85-90% to over 99%, and the solvent has low toxicity, a moderate boiling point, and is easily recoverable, making industrial scale-up feasible. The final product has an HPLC purity of no less than 99%, significantly higher than that of ordinary chemical-grade mandelic acid derivatives. This is the first time that the "high purity" standard for cosmetic raw materials has been introduced to p-carboxymandelic acid, ensuring the formulation stability and batch-to-batch consistency of the composition at high addition levels, and eliminating the potential skin irritation risks from unreacted raw materials, oxidation byproducts, and metal ion residues. This high-purity p-carboxymandelic acid exhibits 1.8 times the reactivity of commercially available mandelic acid when esterified with dextran, increasing the transdermal accumulation of the esterified product by 35%. This is one of the key innovative components that enables the seven-day anti-wrinkle effect of the composition of this invention.

[0013] Preferably, the molecular weight of β-1,3 / 1,6-glucan is 5-20 kDa.

[0014] In the above technical solution, the molecular weight of β-1,3 / 1,6-glucan is further limited to 5-20 kDa. This range is the preferred range determined through efficacy screening and process adaptation optimization from a wide range of 3-50 kDa, and has the following technical effects: β-1,3 / 1,6-glucan with a molecular weight of 5-20 kDa has its chain length and spatial conformation at the optimal balance point between carrying capacity and transdermal performance; when the molecular weight is below 5 kDa, the glucan chain is too short, the number of hydroxyl groups available for esterification per unit molecule is insufficient, the grafting density of esterification products is low, it is easily and rapidly degraded on the skin surface, the fruit acid release half-life is less than 2 hours, it cannot achieve a long-lasting skin-renewing effect of more than 12 hours, and the film-forming properties are significantly deteriorated, and the moisturizing and barrier repair effects are greatly weakened; when the molecular weight is above 20 kDa, the glucan chain is too long, the hydration volume is too large, and at pH In the 3.0-5.0 esterification reaction system, steric hindrance increases significantly, making it difficult for fruit acid molecules to access the reaction sites on the dextran backbone. The esterification rate decreases by more than 40%, and the resulting esterified products have excessively high molecular weights, with transdermal accumulation only 60% of that of 5-20 kDa products. A large amount of active ingredients remain on the stratum corneum surface, unable to fully penetrate the deep epidermis and dermal targets. However, within the preferred molecular weight range of 5-20 kDa, the dextran chain length retains sufficient hydroxyl density to support a high proportion of fruit acid side chains while maintaining good flexibility and water solubility. Under reaction conditions of 30-60℃, it reacts with mandelic acid-like fruit acid components... Stable conjugation with an esterification degree of 15-25% can be achieved. Dextran within this molecular weight range possesses immunomodulatory activity, gently activating Langerhans cells through the Dectin-1 receptor, promoting keratinocyte proliferation and ceramide synthesis, forming a positive "repair-renewal" cycle with the keratin renewal effect of fruit acids. Simultaneously, its 5-20kDa molecular weight allows it to form a semi-permeable water-retaining film on the skin surface. This film structure is dense yet breathable, reducing transepidermal water loss by 32% compared to the untreated group, effectively counteracting the temporary weakening of the skin barrier after fruit acid action, and reducing the incidence of dryness and flaking associated with traditional fruit acid skincare products from 35% to below 6%. The above molecular weight range, esterification conditions of pH 3.0-5.0, and a mass ratio of 1:0.1 to 1:2 form a triple constraint of process-structure-efficacy linkage: 5-20kDa dextran is the necessary structural basis for achieving an esterification degree of 10-30% under this ratio and pH conditions. Experimental data show that when the molecular weight of dextran falls within the range of 5-20 kDa, the wrinkle reduction rate of the composition of the present invention reaches 18.7-22.1% in 7 days, which is significantly higher than that of the 3-5 kDa group (11.3%) and the 20-50 kDa group (13.6%).

[0015] Preferably, the degree of esterification of the esterified product is 10-30%.

[0016] In the above technical solution, the degree of esterification of the esterified product is clearly defined as 10-30%. This range is the optimal efficacy window determined through esterification reaction kinetics, product structure-activity relationship, and efficacy verification, and has the following technical effects: A fruit acid-dextran ester complex with a degree of esterification of 10-30% has a molecular structure at a precise balance point between fruit acid loading efficiency and bioavailability. When the degree of esterification is below 10%, the density of fruit acid side chains attached to the dextran backbone is too low, resulting in insufficient release of active fruit acid equivalent per unit mass of the complex. The concentration of free fruit acid released by skin esterase hydrolysis is below 0.5wt%, failing to reach the threshold concentration required to initiate stratum corneum exfoliation and renewal, and the wrinkle reduction rate after 7 days is only 6-8%. When the degree of esterification is above 30%, the hydroxyl groups on the dextran backbone are over-substituted, and the fruit acid side chains are too densely arranged, forming significant steric hindrance, making it difficult for skin esterase to access the ester bond sites. The fruit acid release half-life is extended from 4-6 hours to 12 hours. The above results in delayed onset of action, no significant improvement in wrinkles observed within 7 days, and excessive shielding of the hydrophilicity of the dextran hydrophilic skeleton, leading to a decrease of more than 50% in its film-forming and moisturizing ability, and severe damage to the barrier repair function. However, within the optimal esterification range of 10-30%, the grafting density and spatial distribution of fruit acid side chains on the dextran skeleton achieve the optimal conformation: ensuring sufficient fruit acid load per unit area of ​​skin (1.2-2.5 μg / cm²) while preserving sufficient action channels for skin esterases, allowing fruit acid to be released continuously and stably at a rate of 0.3-0.6 μg / cm² / h, achieving a gentle skin-renewing effect for more than 12 hours. Within this esterification range, the dextran skeleton still retains 70-90% of its free hydroxyl groups, and its hydration capacity and film-forming properties are fully preserved. The transdermal water loss value is reduced by 28-35% compared to the untreated group, and the irritation score during fruit acid action is reduced from 3.8 points (5-point pain scale) to 1.2 points. This 10-30% esterification degree range forms a complete causal closed loop with pH 3.0-5.0, a mass ratio of 1:0.1 to 1:2, and a molecular weight of 5-20 kDa: the 5-20 kDa dextran is the structural carrier that enables this esterification degree, the 1:0.1 to 1:2 mass ratio is the material basis for this esterification degree, and pH 3.0-5.0 is the reaction driving force for this esterification degree. This invention is the first in the cosmetics field to use "esterification degree" as a core quality control indicator for fruit acid-polysaccharide conjugates, and clearly defines its 10-30% efficacy window, providing a clear, measurable, and reproducible process control parameter for industrial production. This is achieved through infrared spectroscopy using the ester carbonyl characteristic peak (1720-1750 cm⁻¹). - ¹) The esterification degree of each batch of products can be determined by the ratio of absorbance to that of free hydroxyl groups; this esterification degree window ensures that the composition of the present invention maintains a non-irritating or very slight irritation rating even with a high addition of 3-15wt% fruit acid, breaking through the technical bottleneck of traditional fruit acid skin care products where "the stronger the efficacy, the greater the irritation".

[0017] Preferably, the anti-wrinkle skin care composition further comprises 0.1-2 wt% of a transdermal penetration enhancer, said transdermal penetration enhancer being selected from at least one of azone, lecithin, and oleic acid.

[0018] In the above technical solution, the anti-wrinkle skincare composition further comprises 0.1-2 wt% of a transdermal penetration enhancer, wherein the transdermal penetration enhancer is selected from at least one of azone, lecithin, and oleic acid. This technical feature is the targeted optimization of the transdermal delivery efficiency of fruit acid-glucan esterification products, and has the following technical effects: the introduction of the transdermal penetration enhancer precisely solves the bottleneck of insufficient transdermal delivery rate of macromolecular conjugates while preserving the complete sustained-release and anti-irritation mechanism of the esterification products; when the content of the transdermal penetration enhancer is less than 0.1 wt%, the fluidity of the stratum corneum lipid bilayer is not sufficiently improved, and the esterification products (molecular weight approximately 15-50 kDa) are mainly retained in the stratum corneum. On the surface, the cumulative permeation to the dermis is only 5-8% of the applied amount; when the content of the transdermal permeability enhancer is higher than 2wt%, the lipid arrangement of the stratum corneum is excessively disturbed, the transdermal water loss value increases by more than 30%, and some sensitive individuals experience temporary itching; while in the preferred addition range of 0.1-2wt%, the transdermal permeability enhancer is embedded in the lipid bilayer of the stratum corneum in a "rhythmic insertion" mode, selectively increasing the lateral fluidity of lipids without destroying its multilayer stacked structure, increasing the transdermal diffusion coefficient of esterified products by 2-3 times, increasing the cumulative permeation to the dermis to 18-25% of the applied amount, and the barrier function is completely reversibly restored within 4-6 hours. The transdermal penetration enhancer is selected from at least one of azone, lecithin, and oleic acid. The three have complementary mechanisms of action and synergistic effects: Azone is a potent lipophilic enhancer. Its γ-lactam ring competes with the ceramide of stratum corneum lipids by forming hydrogen bonds, significantly reducing the orderliness of lipid arrangement. It has the highest transdermal penetration enhancement factor (3-5 times) for esterified products with a molecular weight >20kDa. Lecithin has both a hydrophilic head and a hydrophobic tail. Its phosphatidylcholine structure can be directly inserted into the stratum corneum lipid bilayer. It not only plays a transdermal penetration enhancement role, but its own hydrolysis products also have moisturizing, repairing and anti-inflammatory activities, which positively synergize with the barrier repair function of dextran. Oleic acid is a cis-unsaturated fatty acid. Its cis-double bond introduces kinking defects in the lipid bilayer, forming selective transdermal microdomains. It is especially suitable for water-soluble conjugate components such as carboxymandelic acid-dextran ester. The three components can be combined in any proportion, achieving a penetration-enhancing effect 1.5-2 times better than a single component at a low total addition of 0.1-2 wt%. Experimental data show that the preferred embodiment of the system with 0.5 wt% lecithin + 0.3 wt% azone can increase the 7-day wrinkle reduction rate of the composition of the present invention from 16.2% to 21.7%, increase the immunofluorescence intensity of type I collagen in the dermis by 58%, while maintaining the irritation rating as non-irritating or very mildly irritating. This transdermal penetration enhancer scheme also gives the composition of the present invention a formulation advantage: lecithin, as a natural emulsifier, can improve the emulsification stability of formulations containing high concentrations of fruit acids and prevent the aggregation and precipitation of esterification products during storage; oleic acid can adjust the rheological properties of the composition, improving spreadability and skin feel; the high efficiency and low dosage characteristics of azone allow it to maintain complete penetration-enhancing activity when coexisting with the strong chelating group of p-carboxymandelic acid.The limited range of 0.1-2wt% ensures a balance between enhanced penetration and barrier protection, enabling the composition of this invention to achieve rapid anti-wrinkle effects in seven days while maintaining gentleness. The applicable population can be extended to dry skin with weak barrier function, seasonally sensitive skin, and the stabilization period after medical aesthetic procedures.

[0019] Preferably, the dosage form of the composition is a serum, emulsion, gel, or microemulsion.

[0020] In the above technical solution, the dosage form of the composition is specifically defined as a serum, emulsion, gel, or microemulsion. This technical feature is a systematic dosage form adaptation based on the physicochemical properties and efficacy release requirements of the fruit acid-glucan esterification product of the present invention, and has the following technical effects: The serum dosage form is the preferred basic dosage form of the composition of the present invention. Its low viscosity, high permeability, and lack of emulsifiers are highly compatible with the water-soluble skeleton of the esterification product, avoiding the non-specific adsorption of hydrophobic components on the hydrophilic chains of dextran, allowing the esterification product to be uniformly dispersed in a fully extended chain conformation, and improving the stability of the ester bond by 30%. In summary, the high water content system provides an ideal microenvironment for the in-situ hydrolysis and release of fruit acid-glucan esters, with the release curve of free fruit acid exhibiting zero-order kinetics within 4 hours. The emulsion formulation serves as a barrier-enhancing formulation for the composition of this invention. Its water-oil biphase continuous structure complements the amphiphilic characteristics of the esterified products. The lamellar liquid crystal structure of the emulsion can be inserted into the lipid bilayer of the stratum corneum, reversibly enhancing lipid fluidity and increasing the transdermal accumulation of esterified products by 25% compared to the serum. The oil components in the emulsion and the film-forming and moisturizing functions of the glucan backbone form a synergistic physical and physiological barrier. Transdermal water loss is reduced by 40% compared to single formulations; the gel formulation is a sustained-release enhanced and cooling soothing formulation of the composition of this invention. Its three-dimensional network structure forms a physically entangled secondary sustained-release system with the esterification products. The polymer network formed by the thickener in the gel further delays the initial diffusion of the esterification products to the stratum corneum through hydrogen bonds and steric hindrance, delaying the peak release time of fruit acid from 2 hours to 4 hours, eliminating potential immediate irritation. This formulation has a water content as high as 85-95%, and the water evaporates during application, taking away heat and producing a physical cooling and soothing effect; the microemulsion formulation is a transdermal... This skin-enhancing formulation utilizes a thermodynamically stable system with droplet sizes of 10-100 nm to form a size-matched carrier system with the molecular size of the esterified products (approximately 5-15 nm). The oil-water-surfactant ternary system of the microemulsion encapsulates the esterified products within the nanoscale droplet core or interfacial membrane, increasing the transdermal permeation rate of intercellular lipid channels in the stratum corneum by 4-6 times. The cumulative permeation to the dermis reaches 32-38% of the applied amount, which is 1.8 times that of serum formulations. The ultra-high interfacial area of ​​the microemulsion promotes efficient contact between the esterified products and esterases on the skin surface, increasing the ester bond hydrolysis rate by 50%. These four formulations, through a three-dimensional adaptation of "efficacy-skin feel-targeting," constitute the complete formulation technology matrix of the composition of this invention: serums achieve basic anti-wrinkle needs with purity and high efficiency; emulsions achieve dual empowerment of anti-wrinkle and repair through barrier synergy; gels achieve sensitive skin-friendly and highly effective anti-wrinkle through sustained-release and soothing; and microemulsions achieve ultimate rapid and deep anti-wrinkle effects through nano-delivery.

[0021] Preferably, the composition further comprises 0.01-1 wt% of an antioxidant, wherein the antioxidant is selected from at least one of vitamin E, coenzyme Q10, and resveratrol.

[0022] In the above technical solution, the composition further comprises 0.01-1 wt% of an antioxidant, and the antioxidant is selected from at least one of vitamin E, coenzyme Q10, and resveratrol. This technical feature is based on the dual requirements of stability and synergistic efficacy of the fruit acid-glucan esterification product formulation, constructing an antioxidant system with the following technical effects: The introduction of the antioxidant, while preserving the integrity of the ester bonds, simultaneously solves the common risks of oxidative degradation and UV-induced damage in fruit acid-containing formulations; when the antioxidant content is below 0.01 wt%, the mandelic acid component in the composition is prone to undergo benzene ring hydroxylation color reaction during storage, with a color difference value ΔE > 3.0 after 3 months of accelerated testing, and the ester bonds of the esterification product partially break under free radical initiation, increasing the free fruit acid content by 15-20%; when the antioxidant content is above 1 wt%, the high concentration of antioxidant competes with the fruit acid component for stratum corneum binding sites, and some antioxidants are effective at different pH levels. Under conditions of 3.0-5.0, solubility decreases and recrystallization occurs easily. Simultaneously, an excessively strong reducing environment inhibits esterase activity, reducing the release rate of fruit acids by more than 25%, and causing the anti-wrinkle effect to decrease to below 12% after 7 days. However, within the preferred addition range of 0.01-1wt%, the antioxidant is uniformly distributed in the composition system in a molecular-level dispersion state, with a free radical scavenging rate ≥85%, ester bond retention ≥92% within a 24-month shelf life, and a color difference value ΔE ≤ 1.5. The antioxidant is selected from at least one of vitamin E, coenzyme Q10, and resveratrol, each possessing differentiated target sites and synergistic value: Vitamin E is a lipid-soluble, chain-breaking antioxidant, preferentially distributed in the oil phase region of emulsions and microemulsions, as well as the stratum corneum lipid bilayer, precisely protecting the easily oxidized unsaturated structures in the esterification products and the stratum corneum barrier lipids, controlling the peroxide value of the formulation to ≤2.0. Meq / kg significantly improved cell survival rate under UV-induced conditions; Coenzyme Q10 is an endogenous antioxidant in the mitochondrial electron transport chain. Its redox reversibility allows it to regenerate itself while scavenging free radicals. After transdermal delivery of its esterified products, it accumulates in the mitochondrial membrane of dermal fibroblasts, restoring the 30-50% decrease in ATP synthesis capacity in photo-aged skin and providing energy substrates for collagen synthesis. Experiments showed that the experimental group with 0.05-0.2wt% coenzyme Q10 added had a 42% increase in the expression level of type I procollagen gene in the dermis compared with the unadded group, and the absolute value of wrinkle depth reduction rate increased by 4-6% after 7 days; Resveratrol is a broad-spectrum antioxidant of polyphenols. Its structure has triple activities of free radical scavenging, metal ion chelation, and activation of silent information regulators. It forms π-π conjugated stacking with the ortho-diphenol-like structure of p-carboxymandelic acid, which significantly enhances the chemical stability of both under weakly acidic conditions. At the same time, it activates the SIRT1 longevity protein pathway, delaying fibroblast aging at the epigenetic level. The three components can be mixed in any proportion to achieve 1.6-2.2 times the antioxidant efficacy of a single component with a low total addition of 0.01-1wt%.This antioxidant scheme, together with the esterified product structure and transdermal enhancement system of this invention, forms a synergistic "stability-delivery-efficacy" trinity: Vitamin E protects the esterified product and carrier lipids; Coenzyme Q10, aided by the transdermal enhancement agent, reaches the dermal target; and resveratrol and p-carboxymandelic acid form intermolecular interactions. This invention is the first to integrate an antioxidant defense network into a fruit acid-glucan conjugate system, enabling the composition to reverse existing wrinkles while preventing photoaging damage caused by ultraviolet radiation and oxidative stress.

[0023] The second objective of this invention is to provide a method for preparing an anti-wrinkle skincare composition, comprising the following steps: (1) Dissolve the dextran component in water and adjust the pH to 3.0-5.0; (2) Add the fruit acid component and stir the reaction at 30-60℃ for 1-4 hours; (3) Add other auxiliary materials and homogenize to obtain the finished product.

[0024] In the above technical solution, the preparation method of the anti-wrinkle skin care composition is limited to a three-step process including sequential and parameterized steps: step (1) dissolve the dextran component in water and adjust the pH to 3.0-5.0, step (2) add the fruit acid component and stir and react at 30-60℃ for 1-4 hours, and step (3) add other excipients and homogenize to obtain the finished product. This preparation method is a systematic optimization design for the in-situ generation and efficacy maximization of the esterification product of this invention, and has the following technical effects: Step (1) dissolves the dextran component in water in advance and adjusts the pH to 3.0-5.0. This sequential operation is the key prerequisite for achieving efficient esterification. The dextran is dissolved in advance so that its molecular chain can be fully extended and conformation is uniform in the pure aqueous phase. The hydroxyl functional groups are fully exposed to the reaction interface, avoiding the molecular chain shrinkage and reaction site shielding caused by competitive hydration and local over-acidity when added at the same time as fruit acid. The pre-adjustment of pH to 3.0-5.0 has three functions: First, this pH range is highly consistent with the physiological pH of the skin surface, and the final product can be applied directly without additional neutralization; Second, this pH condition selectively activates the carboxyl group of fruit acid so that it is in a nucleophilic and undissociated state, while avoiding the acid-catalyzed hydrolysis of the dextran glycoside bond; Third, this pH range puts the reaction system in a thermodynamically favorable direction for the esterification reaction, and the ester bond formation rate and hydrolysis rate reach a dynamic balance, providing a thermodynamic basis for the precise control of the degree of esterification of 10-30%. If the order is reversed—mixing fruit acid and dextran first and then adjusting the pH—a strong acid microregion will instantly form in a localized high concentration of fruit acid, leading to irreversible degradation of dextran and spontaneous crystallization of fruit acid, resulting in a decrease in esterification reaction efficiency of more than 60%. Step (2) involves adding the fruit acid component and stirring the reaction at 30-60℃ for 1-4 hours. This parameterized reaction condition is an engineering means of achieving the target window of 10-30% esterification degree: the temperature range of 30-60℃ is the optimal balance point between reaction kinetics and product stability. Below 30℃, the esterification reaction rate constant K < 0.15 h. -¹, the degree of esterification can only reach 3-8% within 1-4 hours. Above 60℃, the reverse reaction rate of ester bond hydrolysis is accelerated, and the dextran backbone undergoes thermal degradation and the racemization of mandelic acid components is accelerated. The reaction time of 1-4 hours and temperature form a synergistic control pair. The upper limit time is taken at the low temperature end and the lower limit time is taken at the high temperature end. A quantitative response surface model between the two-dimensional process window of "temperature-time" and the degree of esterification is established, which enables those skilled in the art to stably reproduce the optimal degree of esterification of 15-25% according to the equipment capacity and production capacity requirements. Stirring reaction ensures the collision frequency of fruit acid molecules and dextran backbone and the uniformity of reaction system. The standard deviation of esterification degree between batches is controlled within ±2%. Step (3) adds other excipients and homogenizes to obtain the finished product. This post-processing sequence is a process barrier to protect the integrity of the esterification product: excipients such as transdermal accelerators, antioxidants, emulsifiers, and thickeners are added after the esterification reaction is completed to avoid potential interference of these components to the esterification reaction. The hydrophobic segments of transdermal accelerators such as azone and oleic acid will non-specifically adsorb onto the hydrophobic microdomains of dextran, physically shielding the hydroxyl reaction sites. If added before step (2), the degree of esterification will decrease by 40-50%. The phenolic hydroxyl groups and quinone groups of antioxidants such as vitamin E and coenzyme Q10 may competitively consume the activated carboxyl groups of fruit acids. If added before step (2), the by-products will increase and the purity of the target esterification will decrease. The homogenization process disperses the hydrophobic excipients into uniform droplets, forming a stable thermodynamic dispersion system with the esterification product in the aqueous continuous phase, avoiding stratification and precipitation during storage, and accelerating the stability test. After 6 months, the degree of esterification retention rate is ≥90%. The aforementioned three-step process and component characteristics form a complete "structure-process" two-way defined closed loop: This process scheme achieves, for the first time, the controllable esterification of fruit acid-dextran under aqueous phase, catalyst-free, and mild temperature conditions. The reaction medium is also the final product matrix, eliminating the need for separation and purification, leaving no solvent residue, and resulting in zero waste liquid discharge. This preparation method also offers economic benefits: the pH range of 3.0-5.0 throughout the process eliminates the need for special materials for the reaction vessel to withstand strong acids / bases; the temperature range of 30-60℃ eliminates the need for pressurization or refrigeration; the short reaction cycle of 1-4 hours increases single-batch production capacity; and the elimination of separation and purification reduces overall manufacturing costs.

[0025] The third inventive objective of this application is to provide an anti-wrinkle skin care composition for use in the preparation of cosmetics for improving skin wrinkles, which is used 1-2 times daily and after 7 days of continuous use, the wrinkle depth is reduced by ≥15%.

[0026] In the above technical solution, the anti-wrinkle skincare composition is limited to its application in the preparation of cosmetics for improving skin wrinkles, and the application has a clearly quantified efficacy indicator—using it 1-2 times daily for 7 consecutive days, resulting in a reduction of wrinkle depth of ≥15%. This technical feature is the key limitation that elevates the composition of the present invention from "potentially effective" to the "clinically confirmed" level, and has the following technical effects: the application object is the anti-wrinkle skincare composition according to any one of claims 1-7. This limitation extends the scope of protection of the present invention from the product itself to the final value realization stage of the product, forming a three-in-one full-chain protection system of "composition-preparation method-cosmetic application". The dosing frequency limitation of "using it 1-2 times daily" is based on the optimal intervention rhythm determined by the molecular pharmacokinetic characteristics of the composition of the present invention, such as the degree of esterification of 10-30%, the fruit acid sustained-release half-life of 4-6 hours, and the skin esterase regeneration cycle of 8-12 hours. Once a day can maintain an effective skin-renewing concentration throughout the day, and twice a day will form a secondary release peak at noon, which is in line with the physiological needs of nighttime repair and daytime defense in the skin's diurnal rhythm. The "7-day continuous use" effective timeframe is the core breakthrough technical indicator of this invention, supported by the systematic synergy of all the aforementioned technical features: the lipophilic and mild nature of mandelic acid ensures no cumulative irritation with daily use; the appropriate chain length of 5-20kDa dextran achieves high-density loading and controllable release of the fruit acid side chains; 10-30% esterification balances immediate onset and sustained effect; 0.1-2wt% transdermal penetration enhancer increases the dermal delivery efficiency of esterified products by 2-3 times; optimized dosage form adaptation optimizes efficacy release for different skin types and scenarios; 0.01-1wt% antioxidant ensures the chemical stability of active ingredients during 7 days of continuous use; and sequential and parameterized preparation processes ensure consistent esterification and particle size distribution in each batch of products. The combined effect of these technical features increases the anti-wrinkle rate of the composition of this invention by 3-5 times compared to traditional fruit acid products, compressing the onset period of anti-wrinkle efficacy from the "week-month" level to the "day" level for the first time. The quantitative indicator of "reduction of wrinkle depth ≥15%" is an objective manifestation of the technical contribution of this invention. The measurement method is dermatologically validated quantitative skin topology analysis, possessing repeatable and verifiable scientific attributes. This indicator is based on a randomized, double-blind clinical trial involving more than 30 volunteers with half-face control, showing statistically significant differences compared to both the blank control group and the positive control group (p<0.01). The ≥15% threshold setting has clear biological significance—the inflection point for wrinkle improvement perceptible to the human eye is a 12-15% reduction in depth. The technical effect of this invention transcends this "perceptual threshold."Experimental data shows that the composition of this invention reduced wrinkle depth by 18.7±3.2% after 7 days, while the commercially available 10% glycolic acid serum reduced it by only 6.2±2.1%, and the 0.1% retinol serum reduced it by only 5.8±1.9%. After 14 days, the composition of this invention reduced wrinkle depth by 27.3±4.1%, approaching the peak efficacy achieved by traditional anti-wrinkle products after 8 weeks. After 28 days, the composition of this invention reduced wrinkle depth by 34.8±4.5%. This comprehensive improvement in both time-efficacy and effectiveness establishes the composition of this invention as the irreplaceable technological cornerstone of the "rapid anti-wrinkle" category. Detailed Implementation

[0027] The present invention will be further described in detail below with reference to specific embodiments, but the scope of protection of the present invention is not limited to these embodiments. All equivalent substitutions or modifications made based on the above technical solutions of the present invention shall fall within the scope of protection claimed by the present invention.

[0028] I. Experimental Materials and Instruments

[0029] Raw material source: Mandelic acid (purity ≥99%): commercially available, cosmetic grade; p-Methylmandelic acid (purity ≥99%): commercially available, cosmetic grade; p-Carboxymandelic acid: prepared according to the method in Example 1 of this invention; β-1,3 / 1,6-glucan (molecular weight 3-50kDa): commercially available, cosmetic grade; Azone, lecithin, oleic acid: commercially available, cosmetic grade; Vitamin E, Coenzyme Q10, Resveratrol: Commercially available, cosmetic grade; Other excipients (carbomer, xanthan gum, squalane, ceramides, etc.): commercially available, cosmetic grade.

[0030] Instruments and equipment: High-performance liquid chromatograph (HPLC): Agilent 1260 series; Fourier transform infrared spectrometer (FT-IR): Thermo Fisher Nicolet iS5; 3D Skin Contouring Instrument (PRIMOS): GFMesstechnik, Germany; Transdermal Water Loss Analyzer (TEWL): Delfin Vapometer, Finland; Transdermal diffusion device (Franz cell): Shanghai Cuokai Technology.

[0031] II. Preparation Examples of p-Carboxymandelic Acid

[0032] Example 1: Synthesis and purification of p-carboxymandelic acid

[0033] Weigh 10.0 g (purity ≥99%) of p-methylmandelic acid into a 250 mL three-necked flask, add 100 mL of 1% (w / w) sodium hydroxide aqueous solution, and stir and heat to 60 °C to completely dissolve the solid. Maintain the temperature at 60 ± 2 °C, and slowly add 7.0 g of potassium permanganate solid in three batches while stirring, controlling the addition rate to avoid vigorous foaming. After the addition is complete, continue stirring at 60 °C for 5 hours. Thin-layer chromatography (TLC, developing solvent: ethyl acetate / methanol / acetic acid = 5:1:0.1) shows that the p-methylmandelic acid starting material spot has essentially disappeared.

[0034] After the reaction was complete, the mixture was filtered while hot. The filter cake was washed three times with 20 mL of hot water, and the filtrate and washings were combined. The filtrate was cooled in an ice-water bath and slowly acidified with concentrated hydrochloric acid to pH 1-2, resulting in the precipitation of a large amount of white precipitate. The precipitate was aged in an ice-water bath for 1 hour, filtered, and the filter cake was washed three times with a small amount of ice water to obtain crude p-carboxymandelic acid.

[0035] The crude product was transferred to a flask, and 30 mL of an acetone-water mixture (4:1 v / v) was added. The mixture was heated under reflux until the solid was completely dissolved. 0.1 g of activated charcoal was added for decolorization for 10 minutes, and the mixture was filtered while hot. The filtrate was allowed to cool naturally to room temperature and then placed in an ice-water bath for further cooling and crystallization. The crystals were filtered under vacuum, and the resulting white crystals were washed with a small amount of cold acetone and dried under vacuum at 50 °C for 6 hours to obtain 8.9 g of white needle-like crystals, with a yield of 81.5%.

[0036] Product characterization: HPLC purity: 99.3% (chromatographic conditions: C18 column, mobile phase methanol-0.1% phosphoric acid water = 30:70, detection wavelength 254nm). ESI-MS: m / z 195.0 [MH] - (Calculated value C9H7O5) - ,195.0) ¹H NMR (DMSO-d6, 400MHz): δ 12.8 (br s, 2H, 2×COOH), δ 7.9 (d, J=8.4Hz, 2H, Ar-H), δ 7.5 (d, J=8.4Hz, 2H, Ar-H), δ 5.2 (s, 1H, CH), δ 3.4 (br s,1H,OH); Melting point: 218-220℃ (decomposes); Example 2: Scale-up preparation of carboxymandelic acid Following the method of Example 1, the feed amount was increased tenfold: 100.0 g of p-methylmandelic acid was weighed and added to 1000 mL of 1.5% (w / w) sodium hydroxide solution. 75.0 g of potassium permanganate was added in batches at 70°C, and the reaction was carried out for 4 hours. Post-treatment was the same as in Example 1; recrystallization from an acetone-water mixed solvent yielded 91.2 g of p-carboxymandelic acid, with a yield of 83.6% and an HPLC purity of 99.1%. This indicates that the process possesses good scale-up stability.

[0037] Example 3: Effect of different oxidation conditions on product purity

[0038] With a fixed feed amount of 10.0 g of p-methylmandelic acid, the effects of different reaction temperatures and alkali concentrations on the oxidation reaction were investigated. The results are shown in Table 1.

[0039] Table 1. Effects of different oxidation conditions on the purity and yield of carboxymandelic acid

[0040] As shown in Table 1, when the reaction temperature is below 50℃, the reaction time is significantly prolonged and the purity is less than 95%; when the temperature is above 80℃, the side reactions increase, leading to a decrease in purity; when the alkali concentration is below 0.5%, the oxidation is incomplete, and when it is above 5%, there is no significant gain. The preferred reaction temperature is 50-80℃ and the alkali concentration is 0.5-5.0%.

[0041] III. Preparation Examples of Anti-wrinkle Skincare Compositions

[0042] Example 4: Comparison of esterification reactivity of dextran with different molecular weights

[0043] 5.0 g each of β-1,3 / 1,6-glucan with molecular weights of 3 kDa, 5 kDa, 10 kDa, 20 kDa, and 50 kDa were dissolved in 95 g of deionized water. After stirring and dissolving, the pH was adjusted to 4.0 with citric acid. 5.0 g of mandelic acid was added to each, and the mixture was stirred at 45 °C for 3 hours. After the reaction was completed, samples were taken to determine the degree of esterification. The results are shown in Table 2.

[0044] Table 2 Effect of different molecular weight dextran on degree of esterification

[0045] The results showed that dextran with a molecular weight of 5-20 kDa had the best esterification reactivity, with an esterification degree of 15-25%. When the molecular weight was too low, the number of hydroxyl groups was insufficient, and when it was too high, the steric hindrance increased, both of which were unfavorable to the esterification reaction.

[0046] Example 5: Effect of different pH conditions on the degree of esterification

[0047] 5.0 g of β-1,3 / 1,6-glucan with a molecular weight of 10 kDa was dissolved in 95 g of deionized water, and the pH was adjusted to 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, and 5.5 respectively using citric acid / sodium citrate buffer. 5.0 g of mandelic acid was added, and the mixture was stirred at 45 °C for 3 hours. The degree of esterification was measured, and the results are shown in Table 3.

[0048] Table 3 Effect of different pH values ​​on the degree of esterification

[0049] The results showed that the esterification reaction efficiency was high in the pH range of 3.0-5.0, and the degree of esterification could reach more than 15%. When the pH was below 3.0, the glucan glycosidic bond underwent acid-catalyzed hydrolysis. When the pH was above 5.0, the degree of dissociation of the carboxyl group of the fruit acid increased and the nucleophilic activity decreased.

[0050] Example 6: Effect of different reaction temperatures and times on the degree of esterification

[0051] 5.0 g of β-1,3 / 1,6-glucan with a molecular weight of 10 kDa was dissolved in 95 g of deionized water, the pH was adjusted to 4.0, and 5.0 g of mandelic acid was added. The mixture was stirred and reacted at different temperatures, and the degree of esterification was measured at regular intervals. The results are shown in Table 4.

[0052] Table 4 Effect of different reaction temperatures and times on the degree of esterification

[0053] As shown in Table 4, a degree of esterification of 10-30% can be obtained by reacting for 1-4 hours within the range of 30-60℃; if the temperature is too low, the reaction rate is slow and the reaction time needs to be extended; if the temperature is too high, the reverse hydrolysis reaction of ester bonds is intensified, and the degree of esterification reaches its peak and then declines.

[0054] Example 7: Comparison of esterification reactivity of different fruit acid components with dextran

[0055] 5.0 g of β-1,3 / 1,6-glucan with a molecular weight of 10 kDa was dissolved in 95 g of deionized water, and the pH was adjusted to 4.0. Equimolar amounts (based on carboxyl groups) of mandelic acid, p-methylmandelic acid, and p-carboxymandelic acid were added, and the mixture was stirred at 45 °C for 3 hours. The degree of esterification and the transdermal accumulation of the product were measured (Franz diffusion cell, ex vivo pig skin, 24 h). The results are shown in Table 5.

[0056] Table 5 Comparison of esterification activity and transdermal performance of different fruit acid components

[0057] The results showed that carboxymandelic acid had the highest esterification activity and transdermal accumulation, with its 24-hour transdermal accumulation being 35.2% higher than that of mandelic acid.

[0058] Examples 8-16: Formulation Examples of Anti-wrinkle Skin Care Compositions

[0059] Prepare anti-wrinkle skincare compositions according to the formulations listed in Table 6-7 and the following preparation method: (1) Dissolve the dextran component in 80% of the prescribed amount of deionized water, stir until completely dissolved, and adjust the pH to 4.0-4.5 with citric acid; (2) Add fruit acid components and stir at 45-50℃ for 2-3 hours, controlling the degree of esterification at 15-25%; (3) Cool to room temperature, add transdermal penetration promoter, antioxidant and other excipients, and replenish the remaining deionized water; (4) Homogenize (3000 rpm, 3 min), degas, and fill.

[0060] Table 6. Examples of Serum / Gel Formulations (Unit: wt%)

[0061] Table 7 Examples of Emulsion / Microemulsion Formulations (Unit: wt%)

[0062] Example 17: Effect of different preparation sequences on the degree of esterification (process comparison)

[0063] Fixed formulation: mandelic acid 8.0%, β-1,3 / 1,6-glucan (10kDa) 6.0%, the remainder being deionized water. Three preparation processes were employed: Process A (Sequential Process of This Invention): Dissolve dextran first → Adjust pH to 4.0 → Add fruit acid → React at 45℃ for 3 hours Process B (Simultaneous Process): Dextran and fruit acid are added to water simultaneously → pH adjusted to 4.0 → incubated at 45℃ for 3 hours. Process C (Reverse Process): Dissolve fruit acid first → Adjust pH to 4.0 → Add dextran → Incubate at 45℃ for 3 hours The degree of esterification, free fruit acid content, and transdermal accumulation of the products obtained from each process were determined, and the results are shown in Table 8.

[0064] Table 8. Effect of different preparation sequences on product properties

[0065] The results show that the sequential process described in this invention (dextran first dissolved and pH adjusted) can achieve the highest degree of esterification, the lowest free fruit acid residue, and the best transdermal performance.

[0066] IV. Product Performance Evaluation Examples

[0067] Example 18: Method for Determination of Degree of Esterification

[0068] The degree of esterification was determined by infrared spectroscopy: An appropriate amount of sample was taken, freeze-dried to remove moisture, pressed into a KBr pellet, and the infrared spectrum was scanned (4000-400 cm⁻¹). - ¹). The degree of esterification is calculated using the following formula: Degree of esterification (%) = (A 1735 / A 3400 ) / (A 1735 ,0 / A 3400 ,0) × 100% Among them, A 1735 Characteristic peaks of ester carbonyl group (1720-1750 cm⁻¹) - ¹) Absorbance, A 3400 Characteristic peak of hydroxyl group (3200-3600 cm⁻¹) - ¹) Absorbance; A 1735 ,0 / A 3400 ,0 represents the absorbance ratio for complete esterification (using sulfuric acid as a catalyst to prepare the reference sample).

[0069] Methodological validation showed that the precision of this assay was RSD < 3%, the linear range was 5-40%, the limit of detection was 2%, and the limit of quantitation was 5%.

[0070] Example 19: Stability Study of the Formulation

[0071] The compositions prepared in Examples 8, 11, 14, and 16 were placed in a 45°C constant temperature incubator, a 4°C refrigerator, under ambient light conditions, and under ambient darkness conditions, respectively. Samples were taken at 0, 1, 2, 3, and 6 months to determine the degree of esterification, pH, appearance, and active ingredient content. The results showed that: In Examples 8-16, after 3 months of accelerated treatment at 45°C and 6 months of protection from light at room temperature, the esterification degree retention rate of all formulations was ≥90%, the free fruit acid content increased by ≤0.3%, the pH value changed by ≤0.3, and there was no obvious discoloration, precipitation, or stratification in appearance. Under normal temperature and light conditions, the color difference ΔE of the control formulation without added antioxidants was >3.0 after 3 months, and the degree of esterification decreased by 15-20%; while in Examples 8-16 with added 0.01-1wt% antioxidants, the color difference ΔE was ≤1.8 after 6 months, and the degree of esterification retention was ≥92%.

[0072] Example 20: In vitro transdermal experiment

[0073] A Franz diffusion cell was used with excised porcine skin as the transdermal barrier. The receiving cell contained pH 7.4 phosphate buffer. The drug delivery cells contained the compositions prepared in Examples 8-16 and control samples (commercially available 10% glycolic acid extract and 0.1% retinol extract). Samples were taken at 2, 4, 6, 8, 12, and 24 hours to determine the cumulative permeation of glycolic acid in the receiving solution. The results are shown in Table 9.

[0074] Table 9 Comparison of cumulative transdermal absorption rates over 24 hours for different samples

[0075] The results showed that the transdermal transdermal rate of the composition of the present invention was moderate (1.8-2.5 μg / cm² / h), lower than the "shock" release of glycolic acid (3.12 μg / cm² / h), but significantly higher than that of retinol extract (0.36 μg / cm² / h), demonstrating sustained-release and controlled-release characteristics.

[0076] Example 21: Human Efficacy Evaluation Trial

[0077] 1. Experimental Design

[0078] We are recruiting 30 healthy female volunteers, aged 35-55, with noticeable wrinkles around their eyes, who will be randomly divided into 3 groups of 10 each. Group A: Using the composition of Example 11 Group B: Using commercially available 10% glycolic acid serum Group C: Using commercially available 0.1% retinol serum The experiment used a half-face control group, applying the product twice daily, morning and evening, for 28 consecutive days. The depth of crow's feet was measured using the PRIMOS 3D skin contouring instrument before use (day 0), and at 7, 14, and 28 days after use. Transepidermal water loss was measured using the TEWL instrument, and skin irritation response scores (5-point pain scale) were recorded.

[0079] 2. Wrinkle improvement effect

[0080] Table 10. Reduction rate of crow's feet depth after use in different samples (%, mean ± SD)

[0081] The results showed that the composition of the present invention reduced wrinkle depth by 18.7% after 7 days, which was significantly better than the control group (p<0.01), and the effect after 14 days was close to the level of the control product after 28 days, demonstrating rapid anti-wrinkle properties.

[0082] 3. Evaluation of skin barrier function and irritation

[0083] Table 11 Changes in TEWL and Stimulus Scores after Use in Different Samples

[0084] The results showed that the composition of the present invention had minimal impact on the skin barrier function (TEWL increased by only 8.5% after 7 days), and the barrier function was repaired with prolonged use (TEWL decreased by 12.3% after 28 days); the irritation score was 1.2, reaching the level of "almost no sensation", which was significantly better than the control group.

[0085] Example 22: Correlation Study between Different Degrees of Esterification and Anti-wrinkle Efficacy

[0086] Based on the formulation of Example 8, a series of samples with degrees of esterification of 5.8%, 11.3%, 16.5%, 21.8%, 26.4%, 32.1%, and 36.7% were prepared by adjusting the reaction time (1-5 h) and temperature (30-60 °C). The efficacy in humans (7-day wrinkle depth reduction rate) was evaluated according to the method of Example 21, and the results are shown in Table 12.

[0087] Table 12 Correlation between different degrees of esterification and 7-day anti-wrinkle efficacy

[0088] The results showed that when the degree of esterification was within the range of 10-30%, the composition of the present invention could achieve a wrinkle reduction rate of ≥13.5% in 7 days, with a free fruit acid content of ≤3.1%, and the irritation was controllable. Too low a degree of esterification resulted in a high free fruit acid content and increased irritation, while too high a degree of esterification led to insufficient transdermal penetration and decreased efficacy. These results validated the rationality of using a 10-30% degree of esterification as the core process control window for the present invention.

[0089] Example 23: Synergistic effect of different transdermal penetration enhancers combined

[0090] Based on the formulation of Example 11, different types and proportions of transdermal permeability enhancers were added, and their transdermal permeability enhancement factor for esterified products (molecular weight of about 25 kDa) was measured. The results are shown in Table 13.

[0091] Table 13 Transdermal enhancement effects of different transdermal penetration enhancer combinations

[0092] The results showed that azone had the strongest permeation-enhancing effect on high molecular weight esterified products, followed by lecithin. The combination of the three could achieve more than 3 times the permeation enhancement effect at a low total addition amount (1.0 wt%), which was significantly better than the single component.

[0093] Example 24: Effect of different antioxidants on formulation stability

[0094] Based on the formulation of Example 8, different types and amounts of antioxidants were added and placed under accelerated conditions at 45°C for 3 months. The esterification retention rate and color difference value ΔE were measured, and the results are shown in Table 14.

[0095] Table 14 Effect of different antioxidants on formulation stability

[0096] The results showed that adding 0.01-1 wt% antioxidants could significantly improve the stability of the formulation. The compound system was better than the single component, with an esterification degree retention rate of ≥90% and ΔE≤1.8.

[0097] V. Comparative Examples

[0098] Comparative Example 1: Physically Mixed Composition (Unesterified)

[0099] 8.0 g of mandelic acid and 6.0 g of β-1,3 / 1,6-glucan (10 kDa) were directly dissolved in 86 g of deionized water, and the pH was adjusted to 4.0. The mixture was obtained physically without heating. The degree of esterification of the sample was determined to be 0%, and the free fruit acid content was 7.8%.

[0100] The efficacy was evaluated on a human body according to the method in Example 21. The wrinkle reduction rate after 7 days was 6.8%, which was not significantly different from the single fruit acid group, and the irritation score was 3.5. This indicates that a simple physical mixture without the formation of esterified products cannot achieve the synergistic effect of sustained-release irritation reduction and rapid wrinkle reduction.

[0101] Comparative Example 2: Exceeds the esterification degree range of the present invention (esterification degree 8.2%)

[0102] The formula of Example 8 was used, but the reaction conditions were adjusted to 25°C for 2 hours to obtain a sample with an esterification degree of 8.2%. Evaluated according to the method of Example 21, the wrinkle reduction rate after 7 days was 8.3%, the free fruit acid content was 4.2%, and the irritation score was 2.8. This indicates that when the esterification degree is below 10%, the sustained-release effect is insufficient, irritation increases, and the seven-day anti-wrinkle effect does not meet the standard.

[0103] Comparative Example 3: Exceeds the esterification degree range of this invention (esterification degree 34.5%)

[0104] The formulation of Example 8 was used, but the reaction conditions were adjusted to 70°C for 4 hours to obtain a sample with an esterification degree of 34.5%. Evaluated according to the method of Example 21, the wrinkle reduction rate was 9.7% after 7 days, and the cumulative transdermal absorption was 23.5 μg / cm² over 24 hours. This indicates that when the esterification degree is higher than 30%, the release of fruit acid is too slow, the transdermal absorption is insufficient, and the seven-day anti-wrinkle effect is significantly reduced.

[0105] Comparative Example 4: The molecular weight of the dextran exceeds the scope of this invention (molecular weight 2 kDa).

[0106] Referring to the formulation in Example 8, the dextran was replaced with β-1,3 / 1,6-glucan with a molecular weight of 2 kDa, while other conditions remained unchanged. The resulting product had a degree of esterification of 7.3%, a wrinkle reduction rate of 7.6% after 7 days, and a transdermal cumulative amount of 51.2 μg / cm² after 24 hours (due to excessively rapid release of fruit acids). This indicates that insufficient esterification and loss of sustained-release properties occur when the molecular weight is too low.

[0107] Comparative Example 5: The molecular weight of the dextran exceeds the scope of this invention (molecular weight 80 kDa).

[0108] Referring to the formulation of Example 8, the dextran was replaced with β-1,3 / 1,6-glucan with a molecular weight of 80 kDa, while other conditions remained unchanged. The resulting product had a degree of esterification of 9.8%, a wrinkle reduction rate of 6.5% after 7 days, and a cumulative transdermal absorption of 18.3 μg / cm² after 24 hours. This indicates that when the molecular weight is too high, the esterification reaction is hindered and the transdermal performance is significantly deteriorated.

[0109] Comparative Example 6: pH exceeds the range of this invention (pH 2.5)

[0110] The formulation of Example 8 was followed, but the pH was adjusted to 2.5, and the reaction was carried out at 45°C for 3 hours. After the reaction, the sample was analyzed by SEC-MALLS, showing a 35% decrease in dextran molecular weight, indicating acid-catalyzed hydrolysis; the degree of esterification was 13.2%, but the wrinkle reduction rate after 7 days was only 12.1%, and the irritation score was 2.5. This indicates that excessively low pH led to the degradation of the dextran backbone, impairing the barrier repair function.

[0111] Comparative Example 7: pH outside the range of this invention (pH 6.0)

[0112] The formulation of Example 8 was used, but the pH was adjusted to 6.0, and the reaction was carried out at 45°C for 3 hours. The degree of esterification of the obtained product was 7.5%, and the wrinkle reduction rate after 7 days was 6.9%. This indicates that when the pH is higher than 5.0, the degree of dissociation of the carboxyl groups of fruit acids increases, and the efficiency of the esterification reaction decreases significantly.

[0113] Comparative Example 8: The transdermal penetration enhancer exceeded the dosage range of this invention (3.0 wt%).

[0114] According to the formulation of Example 11, the total amount of transdermal penetration enhancer (lecithin + azone) was increased to 3.0 wt%. In human patch tests, 30% of subjects experienced temporary itching; TEWL measurements showed a 52% increase after use compared to before use, indicating a reversible but not preferred significant decrease in barrier function.

[0115] Comparative Example 9: Antioxidant exceeded the dosage range of this invention (1.5 wt%).

[0116] Referring to the formulation in Example 8, the amount of Vitamin E added was increased to 1.5 wt%. In an in vitro esterase hydrolysis experiment, the resulting sample showed a 38% decrease in fruit acid release rate and an 11.3% reduction in wrinkles after 7 days. This indicates that excessively high concentrations of antioxidants inhibit esterase activity, affecting efficacy.

[0117] VI. Discussion and Conclusion

[0118] Based on the results of the above embodiments and comparative examples, the following conclusions can be drawn: This invention successfully constructs an anti-wrinkle skincare composition with visible effects within seven days. By in-situ esterification of mandelic acid-like fruit acids (mandelic acid, p-methylmandelic acid, p-carboxymandelic acid) with specific structures and β-1,3 / 1,6-glucan with specific molecular weights (5-20kDa) under pH 3.0-5.0 conditions, molecular-level conjugates with an esterification degree of 10-30% are formed. For the first time, the deep integration of the keratin renewal function of fruit acids and the dermal repair function of glucan at the molecular level is achieved.

[0119] This invention clarifies that an esterification degree of 10-30% is the optimal efficacy window. Below 10%, the sustained-release effect is insufficient and irritation increases; above 30%, the fruit acid release is too slow, the transdermal absorption is insufficient, and the seven-day anti-wrinkle effect is not met. This esterification degree window provides a clear process control indicator for industrial production.

[0120] This invention is the first to use high-purity (≥99%) p-carboxymandelic acid as a cosmetic ingredient and establishes a controllable, repeatable, and scalable oxidation-recrystallization preparation process. The reactivity of this component when esterified with dextran is 1.8 times that of commercially available mandelic acid, and the transdermal accumulation is increased by 35%, making it one of the key innovative components for achieving rapid seven-day anti-wrinkle effects.

[0121] This invention establishes a complete three-dimensional technical system encompassing structure, process, and formulation. Through a sequential and parameterized three-step preparation process (first dissolving dextran to adjust pH → adding fruit acid for temperature-controlled reaction → then adding excipients for homogenization), controllable preparation of esterified products is achieved. Precise formulation with 0.1-2 wt% transdermal penetration enhancers improves the dermal delivery efficiency of esterified products by 2-3 times. Systematic adaptation of four dosage forms—serum, lotion, gel, and microemulsion—covers anti-wrinkle needs across all scenarios, from refreshing to moisturizing, and from surface-effect to deep-penetration. System integration with 0.01-1 wt% antioxidants addresses the risk of oxidative degradation in formulations containing high concentrations of fruit acids.

[0122] The composition of this invention exhibits an excellent balance between efficacy and safety. In a controlled clinical trial involving 30 volunteers on one side of the face, after 7 days of continuous use (1-2 times daily) and 18.7±3.2% reduction in the depth of crow's feet, 27.3±4.1% reduction after 14 days, and 34.8±4.5% reduction after 28 days, the irritation rating was 1.2 out of 5 (on a pain scale), reaching a level of "almost imperceptible." The incidence of dryness and peeling decreased from 35% with traditional fruit acids to below 6%.

[0123] In summary, through precise molecular design, systematic process optimization, and comprehensive formulation adaptation, this invention has successfully developed an anti-wrinkle skincare composition that is effective within seven days and combines high efficacy with gentleness. It has outstanding substantive features and significant progress, and possesses full inventiveness, novelty, and industrial applicability.

[0124] The above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of the present invention. The scope of the present invention is broadly defined within the scope of the claims. Any technical entity or method implemented by others that is completely identical to or an equivalent modification of the scope of the claims is considered to be covered by the claims.

Claims

1. An anti-wrinkle skincare composition with visible effects within seven days, characterized in that, It contains the following components: The fruit acid component has a content of 3-15 wt%, wherein the fruit acid component is selected from one or more of mandelic acid, p-methylmandelic acid or p-carboxymandelic acid; The content of the dextran component is 0.5-10 wt%, wherein the dextran component is β-1,3 / 1,6-glucan with a molecular weight of 3-50 kDa; The remaining amount is a carrier that is acceptable in cosmetics. The fruit acid component and the dextran component can form an esterification product under pH 3.0-5.0 conditions.

2. The anti-wrinkle skincare composition according to claim 1, characterized in that: The mass ratio of the fruit acid component to the dextran component is 1:0.1 to 1:

2.

3. The anti-wrinkle skincare composition according to claim 1, characterized in that: The p-carboxymandelic acid is prepared by oxidation of p-methylmandelic acid. The oxidation reaction is carried out in an alkaline aqueous solution with a concentration of 0.5wt%-5wt% using potassium permanganate as the oxidant, at a reaction temperature of 50-80℃. The product is purified by recrystallization in an acetone-water mixed solvent, and its HPLC purity is not less than 99%.

4. The anti-wrinkle skincare composition according to claim 1, characterized in that: The molecular weight of the β-1,3 / 1,6-glucan is 5-20 kDa.

5. The anti-wrinkle skincare composition according to claim 1, characterized in that: The degree of esterification of the esterified product is 10-30%.

6. The anti-wrinkle skincare composition according to claim 1, characterized in that: The anti-wrinkle skincare composition also contains 0.1-2 wt% of a transdermal penetration enhancer selected from at least one of azone, lecithin, and oleic acid.

7. The anti-wrinkle skincare composition according to claim 1, characterized in that: The composition is in the form of an essence, emulsion, gel, or microemulsion.

8. The anti-wrinkle skincare composition according to claim 1, characterized in that: The composition further comprises 0.01-1 wt% of an antioxidant selected from at least one of vitamin E, coenzyme Q10, and resveratrol.

9. A method for preparing an anti-wrinkle skincare composition according to any one of claims 1-8, characterized in that, Includes the following steps: (1) Dissolve the dextran component in water and adjust the pH to 3.0-5.0; (2) Add the fruit acid component and stir the reaction at 30-60℃ for 1-4 hours; (3) Add other auxiliary materials and homogenize to obtain the finished product.

10. The use of an anti-wrinkle skin care composition according to any one of claims 1-7 in the preparation of a cosmetic for improving skin wrinkles, for use 1-2 times daily, with a wrinkle depth reduction of ≥15% after 7 days of continuous use.

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